13,14-Dihydro-11-deoxy-11-hydroxymethyl-9-deoxy-9-methylene-19-oxo-PGF.sub.1

ABSTRACT

The present invention provides novel 13,14-dihydro-11-deoxy-11-hydroxymethyl-9-deoxy-9-methylene-19-oxo-PGF.sub.1 compounds, which are useful for a variety of pharmacological purposes, e.g., antiasthmatic indications.

CROSS REFERENCE TO RELATED APPLICATION

This application is a division of Ser. No. 025,879, filed Apr. 2, 1979.

BACKGROUND OF THE INVENTION

The present invention relates to novel prostaglandin analogs.Particularly, the invention relates to prostaglandin analogs wherein theC-19 position is substituted by oxo, i.e., 19-keto-PG compounds or19-oxo-PG compounds. Most particularly, the present invention relates tonovel13,14-dihydro-11-deoxy-11-hydroxymethyl-9-deoxy-9-methylene-19-oxo-PGF.sub.1compounds, a disclosure of the preparation and pharmacological use ofwhich is incorporated here by reference from U.S. Ser. No. 025,899,filed Apr. 2, 1979.

PRIOR ART

Prostaglandins exhibiting a variety of substitution at the C-19 positionare known. See particularly J. C. Sih, et al., JACS 91:3685 (1969)wherein 19-oxo-PGE₂ and 13,14-dihydro-19-oxo-PGE₁ are disclosed.Further, Chemical Abstracts 86:43265H purportedly discloses19-oxo-PGF₂α. The abstract is derived from Japanese Kokai 76 82,245.

SUMMARY OF THE INVENTION

The present invention particularly provides:

a compound of the formula ##STR1##

wherein D is

(1) (CH₂)₃ --(CH₂)_(g) --CH₂ --, or

(2) (CH₂)₃ --(CH₂)_(g) --CF₂ --;

wherein g is zero, one, two, or three;

wherein Q is .sub.α -OH:.sub.β -R₅ or .sub.α -R₅ :.sub.β -OH, wherein R₅is hydrogen or methyl;

wherein R₆ is

(a) hydrogen,

(b) alkyl of one to 12 carbon atoms, inclusive,

(c) cycloalkyl of 3 to 10 carbon atoms, inclusive,

(d) aralkyl of 7 to 12 carbon atoms, inclusive,

(e) phenyl,

(f) phenyl substituted with one, 2, or 3 chloro or alkyl groups of oneto 3 carbon atoms, inclusive,

(g) --(p-Ph)--CO--CH₃,

(h) --(p-Ph)--NH--CO--(p-Ph)--NH--CO--CH₃,

(i) --(p-Ph)--NH--CO--(p-Ph),

(j) --(p-Ph)--NH--CO--CH₃,

(k) --(p-Ph)--NH--CO--NH₂,

(l) --(p-Ph)--CH═N--NH--CO--NH₂,

(m) .sub.β -naphthyl,

(n) --CH₂ --CO--R₂₈,

wherein (p-Ph) is para-phenyl or inter-para-phenylene,

wherein R₂₈ is phenyl, p-bromophenyl, p-biphenylyl, p-nitrophenyl,p-benzamidophenyl, or 2-naphthyl, or

(o) a pharmacologically acceptable cation;

wherein R₃ and R₄ are hydrogen, methyl, or fluoro, being the same ordifferent, with the proviso that one of R₃ and R₄ is fluoro only whenthe other is hydrogen or fluoro; and

wherein X is --CH₂ CH₂ --.

The compounds of the present invention are particularly useful forinducing prostaglandin-like biological effects, as described in UnitedStates Ser. No. 026,066. Uses of compounds in accordance with thepresent invention include, therefore, antiasthmatic indications.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention particularly relates to:

13,14-dihydro-11-deoxy-11-hydroxymethyl-9-deoxy-9-methylene-19-oxo-PGF.sub.1; and

13,14-dihydro-11-deoxy-11-hydroxymethyl-9-deoxy-9-methylene-15(R)-19-oxo-PGF₁.

I claim:
 1. A compound of the formula ##STR2## wherein D is (1) (CH₂)₃--(CH₂)_(g) --CH₂ --, or(2) (CH₂)₃ --(CH₂)_(g) --CF₂ --; wherein g iszero, one, two, or three; wherein Q is .sub.α -OH:.sub.β -R₅ or .sub.α-R₅ :.sub.β -OH, wherein R₅ is hydrogen or methyl; wherein R₆ is(a)hydrogen, (b) alkyl of one to 12 carbon atoms, inclusive, (c) cycloalkylof 3 to 10 carbon atoms, inclusive, (d) aralkyl of 7 to 12 carbon atoms,inclusive, (e) phenyl, (f) phenyl substituted with one, 2, or 3 chloroor alkyl groups of one to 3 carbon atoms, inclusive, (g)--(p-Ph)--CO--CH₃, (h) --(p-Ph)--NH--CO--(p-Ph)--NH--CO--CH₃, (i)--(p-Ph)--NH--CO--(p-Ph), (j) --(p-Ph)--NH--CO--CH₃, (k)--(p-Ph)--NH--CO--NH₂, (l) --(p-Ph)--CH═N--NH--CO--NH₂, (m) .sub.β-naphthyl, (n) --CH₂ --CO--R₂₈, wherein (p-Ph) is para-phenyl orinter-para-phenylene, wherein R₂₈ is phenyl, p-bromophenyl,p-biphenylyl, p-nitrophenyl, p-benzamidophenyl, or 2-naphthyl, or(o) apharmacologically acceptable cation; wherein R₃ and R₄ are hydrogen,methyl, or fluoro, being the same or different, with the proviso thatone of R₃ and R₄ is fluoro only when the other is hydrogen or fluoro;and wherein X is --CH₂ CH₂ --.
 2. A compound according to claim 1,wherein R₆ is hydrogen or methyl. 3.13,14-Dihydro-11-deoxy-11-hydroxymethyl-9-deoxy-9-methylene-19-oxo-PGF.sub.1,a compound according to claim
 2. 4.13,14-Dihydro-11-deoxy-11-hydroxymethyl-9-deoxy-9-methylene-15(R)-19-oxo-PGF₁,a compound according to claim 2.